Various substances are extracted from or delivered to the body by many known processes. One method that is often used is the subcutaneous delivery using a needle or other cannula. The use of a needle cannula is an effective method of extracting or delivering a substance but is often painful to the patient. The pain typically experienced by the patient has prompted the development of alternative methods for extracting or delivering drugs.
Various devices have been proposed for introducing substances to the body by transdermal delivery methods. Transdermal delivery devices are often used to provide a sustained release of the drug to maintain a desired rate of delivery. Many transdermal delivery devices are not able to administer drugs at a sufficient rate to be used effectively. Moreover, many drugs can not be delivered transdermally since the drugs are not able to pass through the protective skin layers.
The skin is made up of several layers with the upper composite layer being the epithelial layer. The outermost layer of the skin is the stratum corneum that has well known barrier properties to prevent molecules and various substances from entering the body and analytes from exiting the body. The natural impermeability of the stratum corneum prevents the administration of most pharmaceutical agents and other substances through the skin. The stratum corneum is a complex structure of compacted keratinized cell remnants having a thickness of about 10-30 microns. The stratum corneum forms a waterproof membrane to protect the body from invasion by various substances and the outward migration of various compounds.
Numerous methods and devices have been proposed to enhance the permeability of the skin and to increase the diffusion of various substances through the skin to be utilized by the body. Typically, the delivery of drugs through the skin is enhanced by either increasing the permeability of the skin or increasing the force or energy used to direct the drug through the skin.
One example of a method for increasing the delivery of drugs through the skin is iontophoresis. Iontophoresis generally applies an external electrical field to ionize the drug, thereby increasing the diffusion of the drug through the skin. Iontophoresis can be difficult to control the amount and rate of drug delivery. Under some circumstances, iontophoresis can cause skin damage depending on the extent of ionization, the energy applied to ionize the drug and duration of the treatment.
In recent years there has been an increased interest in micro devices for delivering drugs through the skin is by forming micropores or cuts through the stratum corneum. By penetrating the stratum corneum and delivering the drug to the skin in or below the stratum corneum, many drugs can be effectively administered. The devices for penetrating the stratum corneum generally include a plurality of micron size needles or blades having a length to penetrate the stratum corneum without passing completely through the epidermis. Examples of these devices are disclosed in U.S. Pat. No. 5,879,326 to Godshall et al.; U.S. Pat. No. 5,250,023 to Lee et al., and WO 97/48440.
The micro devices that are commonly used are often manufactured using various techniques such as stereo lithography. These techniques can be used effectively to manufacture devices of a few microns and are able to form channels and other shapes for the delivery of fluids. A disadvantage of the devices is the cost of the manufacturing process and the time required to produce a single item. Other processes such as wet etching, plasma etching and machining can produce fine details in the finished substrate but are not cost or time effective for commercial use.
The prior manufacturing methods and devices for the transdermal administration of drugs have exhibited limited success. Accordingly, a continuing need exists in the industry for an improved device for the administration of various drugs and other substances.